Estrogen induces expression of BCAS3, a novel estrogen receptor-α coactivator, through proline-, glutamic acid-, and leucine-rich protein-1 (PELP1)

We recently reported that the breast carcinoma amplified sequence-3 (BCAS3) gene is regulated by estrogen receptor (ER) α. However, the role of ERα coactivators in the regulation of BCAS3 expression remains unknown, and information regarding the function of the BCAS3 protein is lacking. Here, we define the contribution of ERα coactivators to BCAS3 regulation and identify BCAS3 itself as an ERα coactivator in breast cancer cells. We found that PELP1 (proline-, glutamic acid-, and leucine-rich protein-1), a newly described ERα coregulator, is recruited to BCAS3 chromatin and activates its expression. Analysis of the BCAS3 sequence for functional motifs and evidence from biochemical fractionation suggested that BCAS3 acts as a transcriptional coactivator. Results from chromatin immunoprecipitation, reporter assays, and expression studies further validated the coactivator function of BCAS3 for ERα. BCAS3 physically associated with histone H3 and histone acetyltransferase complex protein P/CAF (p300/CBP-associated factor) and possessed histone acetyltransferase activity. Unexpectedly, BCAS3 required PELP1 to function as a coactivator in ERα transactivation activity. In brief, these results highlight a mechanism whereby ERα activation triggers a positive feedback loop leading to signal amplification in the cell.